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Organ Transplants Without Life-Long Drugs

A new method allowed kidney transplant recipients to eventually stop taking harsh immune-suppressing medications, even though they’d received mismatched organs. These preliminary findings may one day reduce the need for anti-rejection drugs and lead to more options for patients awaiting organ transplants.

Organ transplants are life-saving, but finding well-matched donor organs can be difficult. Patients must also take immunosuppressive drugs for the rest of their lives to keep the immune system from attacking transplanted organs. But these drugs can make it hard to fight off infections. The drugs may also boost the risk for diabetes, cancer and other conditions. Scientists have been searching for new ways to train the immune system to tolerate organ transplants.

Small NIH-funded clinical studies have shown the potential of infusing donor bone marrow cells into transplant recipients. The marrow is home to blood-forming stem cells that generate a variety of immune cells. In some patients, the technique temporarily created a chimeric immune system—a combination of both donor and recipient cells within the body. For a time, these patients better tolerated the donated organs and survived drug-free.

In the new study, scientists led by Dr. Suzanne Ildstad of the University of Louisville set out to create long-term chimerism in kidney recipients. The organs came from unrelated or highly mismatched donors. The research was funded in part by NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

Eight patients had pre-surgical treatment with chemotherapy and radiation to partly knock down their own immune systems. A day after transplant surgery, they received infusions of a complex cellular cocktail derived from the donor’s bone marrow. The mixture included not only blood-forming stem cells but also rare “graft facilitating” cells. These cells, first isolated by Ildstad nearly 20 years ago, are thought to help foreign stem cells get established in recipient bone marrow. The researchers also removed donor immune cells likely to attack the transplant recipient’s own body. This type of immune attack, called graft-versus-host disease, is a common and sometimes deadly complication of bone marrow transplants.

As reported in the March 7, 2012, issue of Science Translational Medicine, one month after transplantation, all 8 patients had a variety of immune cells derived from the kidney donor in their bloodstream. Within a year, 5 of the 8 patients had achieved long-lasting chimerism, with the donated immune cells eventually crowding out the recipient’s own immune cells. By then, these patients had stopped taking immunosuppressant drugs, and their transplanted organs continued to thrive. None of the patients showed signs of graft-versus-host disease.

“The preliminary results from this ongoing study are exciting and may have a major impact on organ transplantation in the future,” says the study’s first author, Dr. Joseph Leventhal of Northwestern Memorial Hospital. “With refinement, this approach may prove to be applicable to the majority of patients receiving the full spectrum of solid organ transplants.”